CO-INHERITANCE OF THE 20210A ALLELE OF THE PROTHROMBIN GENE INCREASESTHE RISK OF THROMBOSIS IN SUBJECTS WITH FAMILIAL THROMBOPHILIA

The presence of the 20210A allele of the prothrombin (PT) gene has rec ently been shown to be a risk factor for venous thromboembolism. This is probably mediated through increased plasma prothrombin levels. The aim of this study was to compare the prevalence of the prothrombin 202 10A allele in control subjects and in subjects with recognised thrombo philia and to establish whether the additional inheritance of the PT 2 0210A allele is associated with an increased risk of venous thromboemb olism. 101 subjects with a history of venous thromboembolism and diagn osed as having either factor V Leiden (R506Q) or heritable deficiencie s of protein C, protein S or antithrombin were studied. The prevalence of the PT 20210A allele in this group was compared with the results o btained for 150 control subjects. In addition, the relationships were examined between genetic status and the number of documented thromboem bolic episodes, and between plasma prothrombin levels and possession o f the PT 20210A allele. 8 (7.9%) of the 101 patients were also heteroz ygous for the PT 20210A allele. This compares with 0.7% in the control subjects (p = 0.005). After exclusion of patients on warfarin, the me an plasma prothrombin of 113 subjects without 20210A was 1.09 U/ml, as compared with 1.32 U/ml in 8 with the allele (p = 0.0002). Among the 101 patients with either factor V Leiden, protein S deficiency, protei n C deficiency or antithrombin deficiency, the age adjusted mean (SD) number of venous thromboembolic episodes at diagnosis was 3.7 (1.5) in those with the PT 20210A allele, as compared with 1.9 (1.1) in those without (p = 0.0001). We have demonstrated that the prevalence of the PT 20210A allele is significantly greater in subjects with venous thro mbosis and characterised heritable thrombophilia than in normal contro l subjects and that the additional inheritance of PT 20210A is associa ted with an increased risk of venous thromboembolism. We have also con firmed that plasma prothrombin levels are significantly greater in sub jects possessing the PT 20210A compared with those who do not.